The present invention relates to the field of peptide drug synthesis, namely a new method of synthesizing GLP-1 peptide agonists.
A new class of diabetic drugs, the GLP-1 or Glucagon-like peptide 1 agonists, are a promising new class of therapeutic compounds. Their preparation by standard solid-phase peptide synthesis techniques is not all that easy, though. Basically, human GLP-1 is a naturally occurring related in sequence to Glucagon. Various, slightly modified engineered sequence variants of natural GLP-1 have been described in literature, with the aim of increasing potency.
Preparation of such GLP-1 peptides has been described in WO 05/027978 and WO 02/90388; however, no better than very basic, standard Fmoc solid phase methodology has been employed for peptide synthesis.
The applicant of the present invention found the approach of the prior art not to allow of good yields which is inacceptable for industrial manufacture. Apparently sequence dependent, individual coupling steps were found to be highly inefficient.
It is the object of the present invention to devise another or improved method of synthesizing GLP-1 peptide agonists.
This object is solved by the method of the present invention comprising the use of a Fmoc-pseudoproline dipeptide unit instead of only single Fmoc-amino acids at a unique interal sequence position during solid-phase synthesis.